It is commonly known that pyrimidine derivatives have a pronounced biological activity and participate in the vital processes of organisms. Pyrimidine derivatives are nucleic bases (uracil, thymine, cytosine), vitamins (thiamine, phosphothiamine), coenzymes (cocarboxylase), growth regulators (orotic acid), etc. [Data for Biochemical Research (3rd ed), R. M. C. Dawson, D. C. Elliott, W. H. Elliott, K. M. Jones (Clarendon Press, 1986].
Of particular interest are systems in which the pyrimidine ring is annelated by other heterocycles. These include purines that are part of nucleic acids (adenine, guanine), folic acid, ATF, pterins, flavins, many other natural substances and their synthetic analogues.
From synthetic derivatives of pyrimidine, substituted barbituric and 2-thiobarbituric acids are among the most widely used in medicine. Data on the biological activity of various derivatives of 5-ylidenebarbituric acids are summarized in the review [2-Sans R G, Chosas M G//Pharmazie, 1988,    Bd 43, N 12, S. 827-829], where the anticonvulsant, antimicrobial, antispasmodic, antipyretic, and anticancer effect of these substances is noted.
High biological activity was also found in annelated pyrimidine derivatives, for example, in pyrazolo[3,4-d]pyrimidines obtained by condensation of 6-hydrazinouracils with iso(thio)cyanates [3-Naka T., Nagaoka A., Furukawa Y., EPO application No. 237289 (1987)], 5-deazaflavines [4-Yoneda F., Sasaki T., Japanese Patent, M cl.C 07D 471/04, No. 03 81276, filed on Aug. 24, 1989 (89/218146), published on May 4, 1991], derivatives of pyrrolo[2,3-d]pyrimidines [5-Quijano M L, Nogueras M., Melguizo M., Alvarez de Cienfuegos G., Melgarejo M., Sanches A.//Nucleosides & Nucleotides, 1989, Vol. 8, N 8, P. 1519-1528], pyrano[2,3-d]pyrimidines [6-Ahluwalia V. K., Batla R., Khurana A., Kumar R.//Indian J. Chem., 1990, Vol. 29B, No. 12, P. 1141] and pyrimido[4,5-c]pyridazines [7-Billings B. K., Wagner J. A., Cook F. D., Castle R. N.//J. Heterocycl. Chem., 1975, Vol. 12, N 6, P. 1221-1224]. The listed compounds possess pesticide, antitumor, antimicrobial, immunosuppressive, nootropic, antihypertensive and antiallergic action.
The above materials indicate the prospect of finding new pharmaceuticals among the pyrimidine derivatives.
At the same time, only a few examples of the formation of a pyrano[2,3-d:6,5-d′] dipyrimidine system are known, in particular, when barbituric acids react with 3-acylchromones [8—Eiden F., Schikorr W.//Arch. Pharm., 1972, Bd 305, N 3, S. 187-193] [9—Stone K. M., Wittington W. L., Treatment of genital gerpes, Rev. of Infect. Dis., 1990, 12, Supl. 6, P.610-619].
There is no information on their biological activity. As noted above, compounds containing a pyrimidinedione fragment have a variety of biological activities. However, the effectiveness of many of the substances studied is not high enough, many of them are toxic and have side effects. In addition, bacteria, viruses and tumor cells very rapidly become resistant to existing drugs [10-Stone K M, Wittington W L, Treatment of genital gerpes, Rev. Of Infect. Dis., 1990, 12, Supl. 6, P.610-619].
A preparation known as Raltegravir has been selected as the prototype of the invention; it is an integrase inhibitor, N-(2-(4-(4-fluorobenzylcarbamoyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl) propan-2-yl) of the following general formula:
(world wide web at accessdata.fda.gov/drugsatfda_docs/label/2011/022145s0181b1.pdf).
The drug inhibits the catalytic activity of HIV integrase, an enzyme involved in viral replication. Inhibition of integrase prevents covalent introduction of the HIV genome into the genome of the host cell in the early stages of infection. Disadvantages of the prototype are associated with the rapidly emerging resistance of viruses to this drug, which causes its low efficiency.